The recent discovery of atrial natriuretic factor (ANF) peptides in mammalian atria that have potent natriuretic, diuretic and vasorelaxant activity has implicated these substances in the control of fluid volume and blood pressure. The proposed research will provide relevant structure-activity data for these peptides with the short term goal of preparing analogs that contain the minimally required amino acid sequence for significant expression of biological activity. From this study we will see if ANF analogs form a basis for rational new therapeutic approaches for treatment of cardiovascular disease. The proposed study will establish a starting point for future analog design with the ultimate goal of obtaining orally active, metabolically stable ANF agonists.